Navegando por Assunto "Chagas disease"

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Anatomopathological aspects of acute Chagas myocarditis by oral transmission
(Sociedade Brasileira de Cardiologia, 2016-07) SOUZA, Dilma do Socorro Moraes de; ARAUJO, Marialva Tereza Ferreira de; SANTOS, Paulo Roberto Silva Garcez dos; FURTADO JUNIOR, Julio Cesar Branco; FIGUEIREDO, Maria Tereza Sanches; PÓVOA, Rui Manuel dos Santos
Vector transmission of Trypanosoma cruzi has declined in Latinpt_B America, which has been attributed to better epidemiological control of this form of transmission, estimated at 8 to 10 million chronic cases, in addition to reducing the number of new cases.1,2 However, there has been an increase in the incidence of acute cases, predominantly by oral transmission due to the ingestion of food contaminated with feces of triatomids, both in isolated cases and in family micro-outbreaks.3 Necropsy studies that describe myocarditis in the acute phase of Chagas' disease are scarce and the existing reports in the literature are of studies carried out in the past decades and involve vector transmission in endemic areas. Cardiac involvement in the acute phase may have varied aspects, especially in relation to myocardial lesion, from an undetectable one, to the evolution to acute heart failure with severe myocarditis and death. Cardiac involvement is present in 90% of the cases, manifesting with myocarditis and pericardial effusion.4,5 The analysis of a series of acute myocarditis cases showed a mortality of 5.6%.
Acesso aberto (Open Access)
Investigação computacional de bromo-ariloxi-2-acetamida etil-benzimidazólicos como inibidores não-peptídicos da proteinase cruzaína de trypanosoma cruzi
(Universidade Federal do Pará, 2017-11-17) FERREIRA, Fábio Jorge de Nazaré; ALENCAR, Nelson Alberto Nascimento de; http://lattes.cnpq.br/3035968396241810; https://orcid.org/ 0000-0002-5763-7024; CARNEIRO, Agnaldo da Silva; http://lattes.cnpq.br/8915348778787525
Chagas’ disease is an infection caused by the Trypanosoma Cruzi flagellated protozoan transmitted by insects (gnat) known in Brazil as “barbeiro” (barber). In the Amazon region, studies have shown that oral contamination has been frequent. The only available drugs for the treatment of Chagas’ disease - Benzonidazole (Rochagan R , Roche) and Nifurtimox (Lampit R , Bayer) - have shown limited efficiency and severe side effects. Cruzain is an enzyme present at all stages of the life cycle of T. cruzi and is the most abundant of the family of papain cysteine proteases found in the parasite, being a promising enzymatic target for the design and development of inhibitors against the disease. Non-peptidic non covalently bound to the enzyme were synthesized and evaluated biologically in vitro and in vivo by Ferreira et al. (2014) analogs of the 8D (or B95) leader compound (crystallographic), yielding a series of active compounds, of which the most powerful are: 8K, 8L and 8R. This work investigated the potential interactions and energies of the cruzain (PDB code: 3KKU) complexed with these four ligands by means of computational tools in order to help elucidate their potential inhibition activity in this enzyme. The computational protocol (parameters, topologies, coordinates, minimizations, thermalizations and productions) was the same for each system. In the final stage of molecular dynamics (MD) production, each system was simulated for a period of 100 ns, to which the mean square deviation (RMSD) stability values of the enzyme and the marked change in 8L ligand conformation were analyzed. The quality of the simulation was also evaluated through potential, kinetic and total energy, volume and temperature graphs. Interactions of hydrogen bonds of the ligands with some amino acid residues belonging to the catalytic site were analyzed. The interaction between the ASP161 and the 8R ligand is emphasized, being ratified by the energy decomposition by residue showing that ASP161 has the best contribution. In terms of binding free energy, the ∆Gtotal follows the experimental trend, pointing the 8R ligand as the most favorable to the reaction having a theoretical value of -30.04kcal.mol−1. This spontaneity is ratified by means of the values obtained with the SIE method, whose theoretical value was -7.54 kcal.mol−1. The results of this work should favor the optimization of compound 8R or development of a series of analogs of this molecule in order to be used as a possible drug for the treatment of Chagas’ disease.